Bipolar illness can be viewed as a clinical disorder of neuronal excitability and modulation, a consistent theme throughout the PI's neuroscience research. The treatment of bipolar disorder is strikingly understudied. This disorder is a priority focus by NIMH due to growing awareness of its severity, chronicity, and complex treatment issues (e.g., PA-93-099: Bipolar Disorder: Clinical, Biological and Treatment Research). The eight week acute phase trial includes adult outpatients, maintained on lithium, randomized (double-blind) to placebo or fluoxetine and provides practical experience managing a randomized controlled trial. The project is designed to develop and apply skills, knowledge and experience in the use of research diagnostic and symptom assessment measures, as well as measures of quality of life and cost to evaluate the effect of treatment. The continuation phase (16 weeks) provides substantive experience in conducting and interpreting longitudinal clinical findings, plus some information on the appropriate duration of continuation treatment and interepisode functioning in bipolar disorder.